Case Report Ind. J Tub.

, 2001, 48, 97

ASYMPTOMATIC APLASTIC ANAEMIA IN A PATIENT RECEIVING

ANTI-TUBERCULOSIS TREATMENT

Anil K. Agarwal, Inder Mohan Chugh, Chandramani Punjabi, Sumita Dewan* and Ashok Shah

(Received on 25.9.2000, Revised Version received on 15.2.2001, Accepted on 22.2.2001)

Summary: Blood dyscrasias with anti-tuberculosis drugs are known but rarely encountered and even less thought of. We
describe a patient who developed pancytopenia due to aplastic anaemia of moderate severity which was diagnosed after
7 months of therapy. This was thought to be an idiosyncratic response to Streptomycin. A 6 month clinical follow-up after
cessation of therapy revealed that the blood counts continued to remain depressed, but she was totally asymptomatic.
Subsequently, we were informed that the patient had an uncomplicated normal vaginal delivery 2 years after stopping
therapy.

INTRODUCTION Widal test resulted in suspicion of typhoid fever for

Blood dyscrasias induced by anti-tuberculosis
drugs are known but are rarely encountered. A wide
range of haematological abnormalities has been
reported with these drugs. However, the physician
rarely suspects this serious complication which can
have fatal consequences. Aplastic anaemia is a
hyporegenerative bone marrow disorder characterised
pathologically by a reduction in the amount of
haemopocitic bone marrow and pancytopenia1. Drugs
are often indicted as a major cause of acquired aplastic
anaemia. We describe a patient who developed
pancytopenia due to aplaslic anaemia of moderate
severity while receiving anti-tuberculosis therapy,
probably caused by an idiosyncratic reaction to
Streptomycin. Although her total leucocytic and
platelet counts were still depressed 6 months after
cessation of drugs, the patient was asymptomatic.
This case report was prompted by the rarity of such
reports in the literature.
CASE REPORT
A 25-year-old female was referred to our
Institute for re-evaluation of anti-tuberculosis therapy
(ATT) initiated 3 months before presentation. Five
months prior to referral, she had developed high grade
continuous fever of acute onset for which she
consulted a general practitioner. She was administered
various courses of antibiotics and symptomatic
treatment but with no relief. A borderline positive
which she received a course of Ofloxacin but without
relief. The patient did not receive Chloramphenicol.
Two months later, she experienced loss of appetite
along with generalised weakness and was then
admitted in a nursing home. A chest roentgenogram
showed right side plcural effusion which was
confirmed on computed tomography (CT) of thorax.
The CT also revealed enlarged right hilar and carinal
lymph nodes. Based on her radiological profile, she
was diagnosed as a case of pulmonary tuberculosis
with pleural effusion and was started on an anti-
tuberculosis regimen comprising Rifampicin 450 mg,
Isoniazid 300 mg, Pyrazinamide 1500 mg and
Ethambutol 800 mg once daily. Ten days after
initiation of ATT, she developed jaundice and her
liver function tests were deranged. Rifampicin and
Pyraziaamide were stopped and Streptomycin
0.75g once daily intramuscularly was added to
Isoniazid and Ethambutol. Oral Prednisolone was
also added which was gradually tapered off. However,
pleural tap was not done. Six weeks subsequent to
rescheduling of the ATT, she felt better and her
symptoms gradually disappeared. She was still on
the three drugs (Streptomycin, Isoniazid and
Ethambutol) when she reported to us.
Physical examination revealed a pale young
female of average built in no acute distress. There
was no clubbing, cyanosis or any significant
lymphadenopathy. Diaphragmatic excursion was
decreased on the right side. Percussion note was dull

Department ot Respiratory Medicine, Vallabhbhai Patel Chest Institute, University of Delhi. Delhi and *Haematologist, Department ot Medicine.
Safdarjung Hospital, New Delhi
Correspondence :Dr. Ashok Shah M.D., Department of Respiratory Medicine. Vallahhbhai Patel Chest Institute. University oi Delhi. P.O. Box 2101.
Delhi-110007
 98
ANIL K. AGARWAL ET AL
and 202 KAU/dL respectively. The liver function
on the right infrascapular and infraaxillary regions tests were within normal limits when she reported to
Breath sounds were decreased in the same areas with us and it continued to remain so. Other investigations
no adventitious sounds. No other abnormality was which included serum proteins, serum calcium blood
detected.
sugar, stool examination, etc. did not show any
abnormality. Tuberculin test with 1 TU did not show
LABORATORY INVESTIGATIONS
any induration. Tests for human immunodeficiency
Haematological investigations, done on virus (HIV) were also negative. Repeated direct
presentation, showed haemoglobin 9.2 g/dL with smear stains for acid fast bacilli were also negative
total leucocyte count 4000/mm’ and differential and the culture did not grow Mycobacterium
leucocyte count: 82% neutrophils, 16% lymphocytes tuberculosis.
and 2% eosinophils. The platelet count was 3,49,0007
CLINICAL COURSE
mm1 and peripheral blood smear showed neutrophilia
along With anisocytosis and microcytosis. Her urine The patient improved clinically with ATT and
examination was within normal limits. A review of her symptoms gradually disappeared. Prednisolone
her haemogram over the preceding 5 months (Table was tapered off and stopped 2 weeks after presenting
1) revealed that at the time of initiation of ATT her to us. Anti-tuberculosis therapy comprising
1
total leucocyte count was 6150/mm and haemoglobin Streptomycin, Isoniazid and Ethambutol was
was 5.4 g/dL for which she received 3 units of blood continued. Rifampicin and Pyrazinamide were
transition which raised the haemoglobin level. Liver introduced 6 weeks later and Streptomycin was
function tests done when she developed jaundice withdrawn 3 weeks later(Figure 1). A chest
showed serum bilirubin of 3.21 mg/dL with SCOT, roentgenogram done at the time of presentation had
SGPT and alkaline phosphatase 115 IU/L, 135 ITj/L shown minimal right side pleural effusion, confirmed
on ultrasonography, which subsequently disappeared.
Haemogram done at the end of the seventh
month of therapy showed a sharp decline in the total
leucocyte and platelet counts. ATT was stopped
forthwith. A bone marrow aspiration (Figure 2)
revealed moderately hypocellular marrow with severe
megaloblastic changes. There were no ring
sideroblasts in the bone marrow. A chest
roentgenogram as well as CT thorax done after
stopping ATT were read as normal. The patient
remained asymptomatic but her total leucocyte and
platelet counts continued to remain depressed even
6 months after cessation of ATT with no untoward
effects. Although the patient was lost to clinical follow
up after 6 months, yet we were informed that she
had an uncomplicated normal vaginal delivery 2 years
after stopping therapy.

DISCUSSION

Blood dyscrasias comprise 10% of the total

number of drug induced adverse effects and account
tor approximately 40% of fatal reactions related to
drug administration2. Although blood dyscrasias are
known to occur with ATT, the adverse effect is not

a 25-year-old female,
 APLASTIC ANAEMIA DURING ANTI-TUBERCULOSIS TREATMENT
99

Table 1: Showing duration and combination of anti-tuberculosis therapy along with haemotological profile
17/3/97 25/3/97 5/4/97 15/4/97 24/5/97 12/6/97 14/10/97 20/10/97 9/12/97 20/1/98 11/4/98
Hb 5.4 6.3 9.9 10.3 8.7 9.2 10.2 10.7 12.1 10.1 11.8

TLC 6150 6200 7050 15300 9450 4000 1800 2000 3100 2400 3490
DLC P73L20 P70L28 P62L35 P83L14 P75L24 P82L16 P69L26 - P73L23 P87L1 1
EOM2 EOM3 E2M1 E1MO E2MO E4M1 - E3M 1 E2M2
PCV 22% - - - 28.4% 29.4% - 28.8% 3.3%
ESR - - 90 120 - 35 49 55
Platelets - - - - 349 116 110 - 194 186

Hb : hameoglobin, P: polymorphonuclear cells, L: lymphocytes, E:eosinophils, M : monocytes

to aplastic anaemia. Although the total leucocyte An idiosyncratic response to a drug is not dose
count (TLC) had fallen to 4000/cu.mm after 3 related. Although it can be seen with the first dose,
months of Streptomycin, Isoniazid and Ethambutol, it seems to occur when patient is exposed to the drug
the platelet count was still normal. However, a sharp on more than one occasion and during prolonged
decline in both the parameters was observed after 7 therapy4. The symptoms may sometimes not manifest
months of ATT, by which time Streptomycin was for weeks or months. There is currently no evidence
withdrawn and Rifampicin and Pyrazinamide added to account for a mechanism regarding the
for 12 weeks. Standard text books1-3 state that the idiosyncratic response to any drug1. This makes it
peripheral blood counts usually return to normal after difficult to investigate adverse drug reactions
withdrawal of the offending drug but, in our case, ascribed to idiosyncracy2.
the counts remained depressed even 6 months after
cessation of therapy, and the patient remained Aplastic anaemia is an uncommon occurrence
asymptomatic. This led us to think that it may have with ATT. In a study of 108 patients with aplastic
been caused by an idiosyncratic reaction to anaemia, only three (2.8%) were found to be taking
ATT2. Williams et aP reported three cases of aplastic
anaemia occurring in association with ATT. All the
three patients died of haemorrhage secondary to
thrombocytopenia, consistent with an irreversible
damage of the bone marrow. The patients were on
different combinations of Streptomycin,
Thioacetazone, Isoniazid, Para-aminosalicylic acid
and Dimethylcarbazine. Deyke and Wallace’1,
reported two cases of aplastic anaemia when using
Streptomycin injections alone, on the 79th and 95*
days of treatment. Of the two patients, one died 19
days after detection while for the other patient, the
recovery was doubtful. Our patient, however,
underwent an uneventful pregnancy, with a successful
outcome, 24 months after cessation of ATT. An earlier
Figure 2: Bone marrow aspiration showing review7 had incriminated Para-aminosalicylic acid
hypocellular marrow fragments and a few and Streptomycin as causative agents for aplastic
haemopoeitic cells (Leishmen’s stain x 40) anaemia. We presume that the idiosyncratic reaction,
in our patient, was due to Streptomycin even though
he had also Isoniazid and Ethambutol. Although
Streptomycin, since this drug has been incriminated
earlier.
100 ANII, K. AGARWAL KT AL
aplastic anaemia due to Streptomycin alone6 and ACKNOWLEDGEMENT
Isoniazid in combination with other drugs2’”1 has been
documented, Isoniazid as the sole cause of aplastic The authors are grateful to Dr. Desh Deepak
anaemia is yet to be reported. The possibility of for composing Figure 1 and Table I.
Ethambutol being the offending agent also remains
open, but to OUR knowledge, there are no reports in REFERENCES
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